1. Field of the Invention
This invention relates to porous, polymer particles useful in chromatography and in various analytical, diagnostic techniques and solid state peptide, DNA synthesis, as well as to processes for preparing the same by use of a template polymerization technique.
2. Description of Related Art
Small, uniformly-sized, cross-linked, porous polymer beads find use as a low-cost, stable adsorbent in separating and purifying organic and inorganic materials including polymers and biomolecules. Such beads will also find use in chromatographic separation, filtration, gel permeation, and affinity chromatography. Further use can be contemplated as microcarriers for cell culture in addition to as supports for solid-phase peptide or DNA synthesis. These beads should be chemically compatible to organic solvents over a wide range of pH and should have a desired shape, size, porosity and surface area.
Macroporous bead polymers of cross-linked copolymers which contain functionality are, for example, are described in J. R. Benson and D. J. Woo, J. Chromatographic Sci., 1984, 22, 386. They are prepared by conventional suspension polymerization. First, a monomeric material and cross-linkers are suspended as droplets in an emulsion (water/a water-immiscible organic solvent) with the aid of a surfactant. With the addition of an initiator, polymerization proceeds in the droplets to form gel beads containing the solvent entrapped within the polymeric matrix. The solvent entrapped is removed by extraction with a second solvent such as benzene, toluene, chloroform, etc., leaving macropores in the polymer matrix. On the other hand, the cross-linked polymer phase forms micropores in the matrix. Desired functionality is provided on the surface of the polymers by dervatization thereof. However, when the polymer is derivatized, functional groups are introduced to the polymer surfaces within micropores as well as within macropores. Because of the porous nature of the polymer matrix, the derivatization reaction takes place indiscriminately within any pore structure. Since the functional groups in the microporous region can interact with analytes, chromatographic separation using the polymer beads prepared by the method described above is undesirably influenced by such micropore derivatization. This normally leads to ill-defined peak shapes such as tailing due to different fluid dynamics in the microporous and macroporous regions. When the beads are used as a solid support in a DNA synthesizer, the chain growth of oligonucleotides can occur in the macroporous region as well as in the microporous region. After several steps of chain elongation, the resultant oligonucleotides would be contaminated by unwanted oligomers.
U.S. Pat. No. 5,047,438 to Feibush and Li describes a method of preparing porous polymer particles by polymerizing monomers and cross-linkers in the pores of inorganic template particles and by removing the inorganic template particles without destruction of the polymer structure. In this process, the surface of the polymer structure can further be modified in various ways to impart desired functionality. One such technique involves bonding a monomer carrying desired functionality to the copolymer surface during polymerization, followed by removal of the template material. However, all the techniques disclosed in U.S. Pat. No. 5,047,438 allow the copolymer surface to be modified uniformly. Therefore, the resulting modified (functionalized) polymer particles would, for example, not be suitable for high-resolution chromatography.
Accordingly, a new porous polymer bead which overcome the above problems associated with the prior art polymer particles is definitely needed. This invention addresses such need by providing uniform, macroporous, functionalized polymer particles prepared by a template polymerization technique entirely different from the techniques taught in the prior art.